A case of Buschke-Löwenstein's tumour presenting with urinary fistula is described. The large lesion in the subpreputial sac occluded the preputial opening and infiltrated beneath the skin of the shaft of the penis resulting in a fungating growth encasing the fistulous tract. The lesion responded well to 25% podophyllin, which is reportedly unusual.
Buschke Lowenstein tumour or giant condyloma acuminata is a rare entity with only less then 50 cases reported in English literature so far. No such case has been reported from the Kashmir valley. They are considered as intermediate lesions between simple condyloma acuminata and invasive squamous cell carcinoma. A 57-year-old heterosexual male presented with a giant perianal condyloma. The lesion was surgically excised completely. Postoperatively patient was put on topical 5-FU ointment. Patient is recurrence free 6 months after surgery. The giant condyloma acuminate is an aggressive tumour with propensity for recurrance and malignant transformation. Surgical excision is the treatment of choice. One such rare case is discussed with review of literature.
Condyloma acuminate; Buschke lowenstein; Perianal
Anogenital warts (condyloma acuminatum or venereal warts) are a common sexually transmitted disease in males and females. Common clinical treatment of anogenital warts is conservative, however, in extreme cases conservative therapy is insufficient and surgical excision is required. Giant condyloma acuminata (Buschke-Löwenstein tumour) is an extremely rare clinical type of genital wart, characterised by aggressive down growth into underlying dermal structures. A 55-year-old female presented with cauliflower-like growth over the anogenital and sacral region, earlier diagnosed as condyloma acuminatum which was resistant to conservative therapy. During the period between 2005 and 2008 the patient underwent five surgical procedures. Due to the size and location of the tumour, gynaecological and plastic surgeons were involved in the procedures. In addition, definitive histology examination identified a superficial vulvar carcinoma.
giant condyloma; Buschke-Löwenstein tumour; vulvar carcinoma; surgery
A 48-year-old man presented with multiple warts in groin for 1 year, which progressively increased in size. Local examination showed large vegetative growth in perianal area. Full thickness excision of involved skin and lesions was undertaken by electrocautery. Entire wound was left open to heal by secondary intention. Histopathological examination suggested Buschke-Löwenstein tumour. Postoperative follow-up for more than 2 years showed the absence of any recurrence.
Buschke-Löwenstein tumour; giant condyloma acuminatum; wide radical excision
We consider approaches to brain dynamics and function that have been claimed to be Darwinian. These include Edelman’s theory of neuronal group selection, Changeux’s theory of synaptic selection and selective stabilization of pre-representations, Seung’s Darwinian synapse, Loewenstein’s synaptic melioration, Adam’s selfish synapse, and Calvin’s replicating activity patterns. Except for the last two, the proposed mechanisms are selectionist but not truly Darwinian, because no replicators with information transfer to copies and hereditary variation can be identified in them. All of them fit, however, a generalized selectionist framework conforming to the picture of Price’s covariance formulation, which deliberately was not specific even to selection in biology, and therefore does not imply an algorithmic picture of biological evolution. Bayesian models and reinforcement learning are formally in agreement with selection dynamics. A classification of search algorithms is shown to include Darwinian replicators (evolutionary units with multiplication, heredity, and variability) as the most powerful mechanism for search in a sparsely occupied search space. Examples are given of cases where parallel competitive search with information transfer among the units is more efficient than search without information transfer between units. Finally, we review our recent attempts to construct and analyze simple models of true Darwinian evolutionary units in the brain in terms of connectivity and activity copying of neuronal groups. Although none of the proposed neuronal replicators include miraculous mechanisms, their identification remains a challenge but also a great promise.
neural Darwinism; neuronal group selection; neuronal replicator hypothesis; Darwinian neurodynamics; Izhikevich spiking networks; causal inference; price equation; hill-climbers
The Improving Outcomes Guidance (IOG) for patients with carcinoma of the penis states that treatment should be provided supraregionally to populations of 4 million or greater who treat over 25 cases of penis cancer each year. This study assesses the impact of this guidance on the management and outcomes of patients with the disease in our region.
PATIENTS AND METHODS
We retrospectively compared the records of 44 patients with carcinoma of the penis treated in our institution between 1969 and 1990 with 101 patients treated between 2002 and 2006, i.e. after supraregional centralisation of the service.
There was no significant change in the stage or grade of the tumours. However, the results show that, in modern times, there was a significant increase in the amount of penis-preserving and nodal surgery as well as a fall in mortality. The improved survival is greatest in patients with poorly-differentiated disease who may, therefore, have benefited from aggressive nodal surgery.
The centralisation of surgery for carcinoma of the penis results in improved outcomes both in terms of preservation and improved survival and this supports the IOG guidance.
Improving Outcomes Guidance; Penis cancer; Penis preservation; Survival
Carcinoma cuniculatum of the penis is an extremely rare variant of squamous cell carcinoma characterized by an endophytic deeply branching and burrowing growth pattern. One documented case series demonstrated afflicted patients ranging in age from 73–83 years with the tumour located on the glans penis, coronal sulcus or foreskin. We report a case of a 55-year-old with disease located on the ventral aspect of the shaft of the penis. The tumour was invasive into the deep dermal connective tissue, comparatively superficial to all previous documented cases. He subsequently underwent a partial penectomy. The case is discussed with a brief review of the literature.
To highlight the salient features of metastatic malignancies involving the penis, with special reference to the primary tumour sites, metastatic mechanisms, clinical features, differential diagnosis, treatment and prognosis.
A comprehensive search of the literature was performed using MEDLINE and EMBASE, using the keywords 'penis', 'secondary malignancy', 'metastasis' and 'malignant priapism' to identify reviews and case reports of secondary penile malignancy. A case of rare clinical presentation of metastatic penile lesion is presented along with the review of the literature.
Secondary malignancy of the penis is a rare clinical entity, despite the rich vascularisation of this organ. The majority of metastatic lesions take their origin from the neighbouring genito-urinary organs, mainly prostate and bladder. These lesions are often associated with disseminated malignancy and hence have a poor outcome. Nodular or ulcerative lesions involving the corpora cavernosa or priapism are the main modes of clinical presentation. In most cases, only palliative or supportive therapy is indicated.
A 73-year-old male presented with a 3-month history of two penile masses: one on the shaft and one on the glans penis. Both lesions were poorly defined, fixated and without tenderness. The sizes were 1.0 × 1.0 × 1.0 cm and 1.2 × 1.5 × 1.5 cm, respectively. The patient underwent lumpectomy of the glans penis; we confirmed malignant lymphoma of the glans penis (B-cell derived; diffused large B-cell) by postoperative pathological examinations. CHOP (cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone) chemotherapy was administered. The patient was tumour-free at the 33-month follow-up.
Cancer of the penis is a rare tumour in Europe and mainly affects the elderly patient population. The aim of this paper was to analyse and study the characteristics of this tumour, in our patient population.
Materials and Methods. A retrospective study was conducted on penile tumours diagnosed and treated in the Urology Department of the Hospital Universitario La Paz, Madrid, in the last ten years.
Results. A total of 34 patients were diagnosed and treated. The mean age at presentation was 71.27 years. The mean time between symptoms and the first consultation was 12.54 months with a median of 6 months. The most common form of presentation was balanoposthitis (32%) and the most common site in our series was the glans. Partial penectomy was performed in 22 cases, total amputation in 8, and local excision in 3. Discussion. Carcinoma of the penis is a pathology which mostly affects elderly patients; in our series, the highest incidence was observed in patients in the group aged 75–84 years. The most common histological type was epidermoid carcinoma in its various forms of presentation. We recorded a mortality of 23%. Conclusion. Penile carcinoma is a rare pathology which affects elderly persons and is diagnosed late.
Magnetic resonance based volumetric measures of hippocampal formation, amygdala (A), caudate nucleus (CN), normalised for total intracranial volume (TIV), were analysed in relation to measures of cognitive deterioration and specific features of memory functions in 18 patients with probable Alzheimer's disease. Neuropsychological examination included the mini mental state examination (MMSE), the Mattis dementia rating scale (DRS), tests of executive functions, assessment of language abilities and praxis, the Wechsler memory scale (WMS), the California verbal learning test (CVLT) and the Grober and Buschke test. The volume of the hippocampal formation (HF/TIV) was correlated with specific memory variables: memory quotient and paired associates of the WMS; intrusions and discriminability at recognition for the Grober and Buschke test. By contrast, except for intrusions, no correlations were found between memory variables and the volume of amygdala (A/TIV). No correlations were found between the volume of caudate nuclei (CN/TIV) and any neuropsychological score. The volume of the hippocampal formation was therefore selectively related to quantitative and qualitative aspects of memory performance in patients with probable Alzheimer's disease.
Verrucous carcinoma of the skin and mucosa is an uncommon type of well-differentiated squamous cell carcinoma. When it is present in the genitoanal region the term used is Buschke-Lowenstein tumor. The human papillomavirus seems to be implicated in its aetiology. Treatment is controversial. Topical chemotherapy, radiotherapy, immunotherapy and radical surgery have been employed.
We report a rapidly progressing penile verrucous carcinoma which was treated sucessfuly with conservative surgery and CO2 laser.
Treatment with CO2 laser in combination with conservative surgery may be a therapeutic option in Buschke-Lowenstein tumor.
condylomata acuminata; lasers; penile neoplasms; squamous cell carcinoma; verrucous carcinoma
Craving for alcohol is a highly controversial subjective construct and may be clarified by Loewenstein's visceral theory, which emphasizes craving's behavioral effects on the relative value of alcohol. Based on the visceral theory, this study examined the effects of a craving induction on the relative value of alcohol as measured by a behavioral choice task. In addition, based on previous evidence of its role in the expression of craving, the influence of DRD4 VNTR genotype (DRD4-L vs. DRD4-S) was also examined.
Thirty-five heavy drinkers (54% male; 31% DRD4-L) were randomly assigned to receive either a craving induction (exposure to personally relevant alcohol cues) or a control induction (exposure to neutral cues), which was followed by an alcohol-money choice task. Participants were assessed for craving and positive/negative affect throughout the procedure, and relative value of alcohol was derived from participant choices for alcohol versus money. DRD4 VNTR status was assessed retrospectively via buccal samples using previously established protocols.
Factorial analysis of the craving induction revealed that it was associated with significant increase in craving (p < .001), but not greater relative value of alcohol. Factorial analyses including DRD4 VNTR genotype of did not suggest an influence on reactivity to the craving induction, although this analysis was substantially compromised by small cell sample sizes. Continuous analyses revealed that craving was significantly associated with the relative value of alcohol (p < .05) and possession of the DRD4-L allele further amplified this relationship (p < .001).
These results are interpreted as generally supporting Loewenstein's visceral theory of craving and evidence of a functional role of DRD4 VNTR genotype in the expression of craving for alcohol. Methodological limitations, mechanisms underlying these findings, and future directions are discussed.
We have reported the molecular cloning, expression, and characterization of a human cellular protein, TAP, which possesses a strong transcriptional activation domain and binds the human immunodeficiency virus type 1 Tat transactivator in vitro and in vivo (L. Yu, Z. Zhang, P.M. Loewenstein, K. Desai, Q. Tang, D. Mao, J.S. Symington, and M. Green, J. Virol. 69:3007-3016, 1995). Here we show that TAP binds the general transcription factor TFIIB. Furthermore, we delineate the binding domains of TAP, Tat, and TFIIB, as well as measure the strengths and specificity of these protein-protein interactions. TAP binds strongly to Tat, with a Kd of (approximately 2 to 5) x 10(-7) M. The Tat activation region contains a 17-amino-acid conserved core domain which is the single contact site for TAP. Single-amino-acid substitutions within the Tat core domain inactivate transactivation in vivo and in vitro and greatly reduce binding of Tat to TAP in vitro. TAP binds strongly to TFIIB, with about the same Kd as for Tat. The interaction between TAP and TFIIB requires a sequence near the carboxy terminus of TFIIB which is also required for binding the strong acidic activator VP16. The contact sites for Tat and TFIIB map within the TAP C-terminal region, which contains the TAP activation domain. These combined results are consistent with the hypothesis that TAP is a cellular coactivator that bridges the Tat transactivator to the general transcription machinery via TFIIB.
The permeability of junctions between cells of the same type (homologous junctions) is greatly increased by retinoic acid (10(-9)- 10(-8) M), a probable morphogen, and this responsiveness is shared by a variety of normal and transformed cell types (Mehta, P.P., J.S. Bertram, and W.R. Loewenstein. 1989. J. Cell Biol. 108:1053-1065). Here we report that the heterologous junctions between the normal and transformed cells respond in the opposite direction; their permeability is reduced by retinoic acid (greater than or equal to 10(-9) M) and its benzoic acid derivative tetrahydrotetramethylnaphthalenylpropenylbenzoic acid (greater than or equal to 10(-11) M). The opposite responses of the two classes of junction are shown to be concurrent; in cocultures of normal 10T1/2 cells and their methylcholanthrene-transformed counterparts, the permeability of the heterologous junctions, which is lower than that of the homologous junctions to start with, falls (within 20 h of retinoid application), at the same time that the permeability of the homologous junctions rises in both cell types. Such a counter-regulation requires a minimum of three degrees of cellular differentiation. A model is proposed in which the differentiations reside in a trio of junctional channel protein. The principle of the model may have wide applications in the regulation of intercellular communication at tissue boundaries, including embryonic ones.
People have present-biased preferences: they choose more impatiently when choosing between an immediate reward and a delayed reward, than when choosing between a delayed reward and a more delayed reward. Following McClure et al. [McClure, S.M., Laibson, D.I., Loewenstein, G., Cohen, J.D. (2004). Separate neural systems value immediate and delayed monetary rewards. Science, 306, 503.], we find that areas in the dopaminergic reward system show greater activation when a binary choice set includes both an immediate reward and a delayed reward in contrast to activation measured when the binary choice set contains only delayed rewards. The presence of an immediate reward in the choice set elevates activation of the ventral striatum, pregenual anterior cingulate cortex and anterior medial prefrontal cortex. These dopaminergic reward areas are also responsive to the identity of the recipient of the reward. Even an immediate reward does not activate these dopaminergic regions when the decision is being made for another person. Our results support the hypotheses that participants show less affective engagement (i) when they are making choices for themselves that only involve options in the future or (ii) when they are making choices for someone else. As hypothesized, we also find that behavioral choices reflect more patience when choosing for someone else.
present-biased preferences; intertemporal discounting; fMRI; multiple systems hypothesis
Extrapulmonary tuberculosis (EPTB) is defined as Mycobacterium TB through Ziehl–Neelsen acid-fast stain and culture in Loewenstein–Jensen in a tissue from a site other than lung parenchyma, in association with clinical or imaging findings compatible with infection locally. The authors report a case of a patient who presented with asthenia, anorexia and weight loss. He complained of fever, chills and night sweats of 1-week duration. The thoracic scan reveals lymph node enlargement in the left axilla and pleural effusion and the histological study revealed a necrotising granulomatous lymphadenitis. It was decided to initiate antituberculous drugs with a good response. EPTB is a difficult diagnostic because lymph nodes contain few tubercle bacilli, leading to a low sensitivity of smear microscopy detection. The introduction of antituberculous agents is the cornerstone of management of such infections and, occasionally, it is the only way to make a diagnosis.
We present a case of a symplastic or "bizarre" leiomyoma of the scrotum. Isolated cases of leiomyomas have been reported arising from the renal pelvis, bladder, spermatic cord, epididymis, prostate as well as the glans penis. However such mesenchymal lesions of the scrotum are very rare.
Macroscopically the tumour was a well-circumscribed grey-white lesion 8.5 cm in size. Because of its peculiar histological characteristics this tumour was assigned as a symplastic or bizarre leiomyoma of the scrotum.
We present this unusual tumour and highlight some important diagnostic and treatment pitfalls related to this rare tumour. This case demonstrates that leiomyomas should be considered in the differential diagnosis of scrotal tumours.
Neonatal circumcision is widely considered to have a protective effect against the development of squamous cell carcinoma of the penis in later life. We report 3 cases of squamous cell carcinoma in men who were circumcised as neonates. The 3 men, aged 49, 55 and 64 years, presented for consideration of brachytherapy. The tumour stage was T3 in 1 case and T1 in the others. The tumours were moderately differentiated in 2 cases and well differentiated in 1 case. All 3 men had a remote history of penile condylomata acuminatum 20–30 years earlier. Oncogenic human papillomavirus (HPV) was found in the tumour specimen in 1 case. All 3 were treated with brachytherapy to the primary tumour on the glans. In 2 cases, subsequent staging inguinal node dissection was indicated because of the grade and stage of the primary tumour. A history of remote HPV infection should increase the index of suspicion for any nonhealing penile lesion, despite a history of neonatal circumcision.
Leiomyomas are benign tumours that originate from smooth muscles. They are often seen in the uterus, but also in the renal pelvis, bladder, spermatic cord, epididymis, prostate, scrotum or the glans penis. Leiomyomas of the tunica albuginea are extremely rare.
A 59-year-old white male has noted an asymptomatic tumour on the right side of his scrotal sac for several years. This tumour has increased slowly and caused local scrotal pain. An inguinal incision was performed, in which the hypoplastic testis, the epididymis and the tumour could be easily mobilized. Macroscopically the tumour showed a solid round nonencapsulated whorling cut surface. Histologically the diagnosis of a leiomyoma was made.
We report here a very interesting and rare case of a leiomyoma of the tunica albuginea. Leiomyomas can be a possible differential diagnosis in this area.
Leiomyoma; Tunica albuginea; Immunohistochemistry
The aim of the study was to describe the shear wave velocity (SWV) values of the penis by virtual touch tissue quantification (VTTQ) and to examine the clinical usefulness of this procedure in evaluation of the rigidity changes in penile erection.
Patients and methods.
VTTQ was performed in 37 healthy volunteers. In the course of erection, SWV values of glans penis, corpus penis and radix penis were quantified and grades of erection were documented. The SWV values at different grades of erection were compared.
The axial and radial SWV values of glans penis, corpus penis and radix penis all significantly decreased from Grade 0 to Grade 4 of erection. At Grade 4, they were less than one-third of that at Grade 0 (axial direction: 0.79 ± 0.13 vs. 2.79 ± 0.32 for glans penis, P<0.001; 0.77 ± 0.19 vs. 2.84 ± 0.30 for corpus penis, P<0.001 and 0.76 ± 0.15 vs. 2.81 ± 0.34 for radix penis, P<0.001; radial direction: 0.82 ± 0.15 vs. 2.83 ± 0.31 for glans penis, P<0.001; 0.79 ± 0.18 vs. 2.81 ± 0.27 for corpus penis, P<0.001 and 0.81 ± 0.16 vs. 2.82 ± 0.33 for radix penis, P<0.001).
VTTQ can provide numerical measurements of penile rigidity and can effectively and sensitively indicate the axial and radial rigidity changes in penile erection, which provide a new approach to assessing the erectile function.
virtual touch tissue quantification; axial and radial rigidity; erection; shear wave velocity
A trial of the action of bleomycin was made on 237 cancer patients with tumours in a visible and actively growing phase who did not require surgery or radiotherapy. Bleomycin was found to have several special properties—absence of haemopoietic toxicity or immunosuppressive action and toxic side-effects affecting skin, mucosae, and lungs. The drug is more effective than drugs previously available for squamous cell carcinoma of the skin and cancer of the penis, the vulva, oesophagus, and uterine cervix, as well as for melanoma and mycosis fungoides. It is at least as effective as those drugs or combinations of drugs previously used for oropharyngeal tumours and testicular dysembryoma or choriocarcinoma. It is very effective when used in arterial perfusion therapy of otorhinolaryngeal tumours. It is of little value in other tumours, in particular for those of the haemopoietic system.
Twenty-four cases of giant condyloma acuminata were found among 100 cases diagnosed as carcinoma of the penis. One of the 24 tumours showed early malignant change. The characteristic histological pattern of giant condyloma consists of broad processes composed of prickle cells associated with little keratinization. The malignant condylomas show, in comparison, a loss of prickle cell preponderance, increased basal cell activity and frequent keratinization, or may present as a solid papillary epithelioma forming broad sheets of uniform cells with many mitoses. The incidence of malignant change in the giant condyloma and the relationship between the benign and malignant tumours are discussed.
Two proprietary semi-permanent hair dyes were tested for carcinogenicity in A and DBAf mice by repeated topical applications in aqueous acetone. Mice of both strains developed lymphoid tumours but experimental differences were marked only in DBAf mice. A number of tumours of the ovary and uterus, and some skin papillomas near the penis, occured in dye-treated but not in control DBAf mice. As many hair-dye constituents are known mutagens, adequate carcinogenicity testing of these substances, and epidemiological study of exposed human populations, are needed for evaluating possible health hazard from hair dyeing.
Larger penis size has been equated with a symbol of power, stamina, masculinity, and social status. Yet, there has been little research among men who have sex with men assessing the association between penis size and social-sexual health. Survey data from a diverse sample of 1,065 men who have sex with men were used to explore the association between perceived penis size and a variety of psychosocial outcomes. Seven percent of men felt their penis was “below average,” 53.9% “average,” and 35.5% “above average.” Penis size was positively related to satisfaction with size and inversely related to lying about penis size (all p < .01). Size was unrelated to condom use, frequency of sex partners, HIV status, or recent diagnoses of HBV, HCV, gonorrhea/Chlamydia/urinary tract infections, and syphilis. Men with above average penises were more likely to report HPV and HSV-2 (Fisher’s exact p ≤ .05). Men with below average penises were significantly more likely to identify as “bottoms” (anal receptive) and men with above average penises were significantly more likely to identify as tops (anal insertive). Finally, men with below average penises fared significantly worse than other men on three measures of psychosocial adjustment. Though most men felt their penis size was average, many fell outside this “norm.” The disproportionate number of viral skin-to-skin STIs (HSV-2 and HPV) suggest size may play a role in condom slippage/breakage. Further, size played a significant role in sexual positioning and psychosocial adjustment. These data highlight the need to better understand the real individual-level consequences of living in a penis-centered society.
penis size; penis satisfaction; condom use; sexually transmitted infections; men who have sex with men (MSM); gay and bisexual men